Helicobacter pylori (H. pylori) infection of human gastric epithelium is a major factor in the development of gastritis and ulcers and may be a risk factor for the development of gastric cancer.sup.1-3. This slender S-shaped gram negative microorganism is routinely recovered from gastric tissue of adults and children with histologic evidence of gastritis or peptic ulceration. Evidence for a causal relationship between H. pylori and gastroduodenal disease comes from studies in human volunteers, gnotobiotic pigs, and germ-free rodents whereby postulates by Koch were satisfied by creating histologically confirmed gastritis following consumption of viable microorganisms.sup.4-11. Although difficult to treat, when eradication is achieved the underlying gastritis resolves and, in patients with duodenal ulcer disease, the recurrence rate of the ulcer decreases dramatically.sup.12.
In spite of in vitro susceptibility to many antimicrobial agents, in vivo long-term eradication of established H. pylori infections with antimicrobial agents is difficult to achieve.sup.18. The microorganism is found within the mucous coat overlying the gastric epithelium. This is a location which does not appear to allow for adequate antimicrobial levels to be achieved when given orally. At the present time, most authorities recommend a "triple therapy", namely a bismuth salt in combination with tetracycline and metronidazole for 2-4 weeks. However, the effectiveness of this or other chemotherapeutic regimens remains suboptimal.
At the present time little is known regarding the role of the mucosal immune system in the stomach. The distribution of Ig producing cells in the normal gastric antrum indicates that IgA plasma cells make up 80% of the total plasma cell population. In addition, the number of plasma IgA cells present in the gastric antrum is comparable to other mucous membranes.sup.25,26. Although a number of studies have looked at immunoglobulin levels in various endocrine fluids, no data is available regarding the concentration of immunoglobulins in gastric secretions. Moreover there is only limited data to suggest that patients infected with H. pylori develop specific IgG and/or IgA antibodies in gastric aspiarates.sup.32. Thus once infection is established, neither antibody nor antibiotics are very effective at eradication.
Czinn et al have shown that repetitive oral immunizations with H. pylori antigens and cholera toxin result in the inducement of a vigorous gastrointestinal IgA anti-H. pylori response in mice and ferrets.sup.18 However, since mice and ferrets are resistant to H. pylori infection and since no small animal model existed at that time to evaluate protection, it was unknown whether the antibodies so formed were protective.
Lee et al have reported the ability to infect germ-free rodents with H. felis and reproducibly document histologic gastritis.sup.9, 10 However no evaluation of protection has been reported.
There remains a need therefore for an effective treatment of H. pylori gastric infection, especially in humans. The present invention seeks to fill that need.